Nanog safeguards early embryogenesis against global activation of maternal ?-catenin activity by interfering with TCF factors.

ABSTRACT: Maternal ?-catenin activity is essential and critical for dorsal induction and its dorsal activation has been thoroughly studied. However, how the maternal ?-catenin activity is suppressed in the nondorsal cells remains poorly understood. Nanog is known to play a central role for maintenance of the pluripotency and maternal -zygotic transition (MZT). Here, we reveal a novel role of Nanog as a strong repressor of maternal ?-catenin signaling to safeguard the embryo against hyperactivation of maternal ?-catenin activity and hyperdorsalization. In zebrafish, knockdown of nanog at different levels led to either posteriorization or dorsalization, mimicking zygotic or maternal activation of Wnt/?-catenin activities, and the maternal zygotic mutant of nanog (MZnanog) showed strong activation of maternal ?-catenin activity and hyperdorsalization. Although a constitutive activator-type Nanog (Vp16-Nanog, lacking the N terminal) perfectly rescued the MZT defects of MZnanog, it did not rescue the phenotypes resulting from ?-catenin signaling activation. Mechanistically, the N terminal of Nanog directly interacts with T-cell factor (TCF) and interferes with the binding of ?-catenin to TCF, thereby attenuating the transcriptional activity of ?-catenin. Therefore, our study establishes a novel role for Nanog in repressing maternal ?-catenin activity and demonstrates a transcriptional switch between ?-catenin/TCF and Nanog/TCF complexes, which safeguards the embryo from global activation of maternal ?-catenin activity.

SUBMITTER: He M 

PROVIDER: S-EPMC7402524 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature